Graft for promoting autogenous tissue growth

ABSTRACT

Surgical repair of diseased or damaged endogenous connective tissue can be accomplished using a tissue graft formed from a delaminated segment of intestinal tissue. The tissue graft comprises the intestinal tunica submucosa, muscularis mucosa and stratum compactum delaminated from the tunica muscularis and the luminal portion of the tunica mucosa. The graft can be conditioned by stretching and formed as a multilayer composition for high tensile strength and resistance to tearing at its points of attachment to existing physiological structures.

FIELD OF THE INVENTION

This invention relates to novel tissue graft constructs and their use topromote regrowth and healing of damaged or diseased tissue structures.More particularly this invention is directed to use of intestinal tissuegrafts as connective tissue substitutes, and most particularly to theiruse in surgical repair of ligaments and tendons and for their use as asurgically applied bone wrap to promote healing of bone fractures.

BACKGROUND AND SUMMARY OF THE INVENTION

Researchers in the surgical arts have been working for many years todevelop new techniques and materials for use as grafts to replace orrepair damaged or diseased tissue structures, particularly bones andconnective tissues, such as ligaments and tendons, and to hastenfracture healing. It is very common today, for instance, for anorthopaedic surgeon to harvest a patellar tendon of autogenous orallogenous origin for use as a replacement for a torn cruciate ligament.The surgical methods for such techniques are well known. Further it hasbecome common for surgeons to use implantable prostheses formed fromplastic, metal and/or ceramic material for reconstruction or replacementof physiological structures. Yet despite their wide use, surgicallyimplanted prostheses present many attendant risks to the patient. Itwill suffice to say that surgeons are in need of a non-immunogenic, hightensile strength graft material which can be used for surgical repair ofbones, tendons, ligaments and other functional tissue structures.

Researchers have been attempting to develop satisfactory polymer orplastic materials to serve as ligament, or tendon replacements or asreplacements for other connective tissues, such as those involved inhernias and joint-dislocation injuries. It has been found that it isdifficult to provide a tough, durable plastic material which is suitablefor long-term connective tissue replacement. Plastic materials canbecome infected and difficulties in treating such infections often leadto graft failure.

In accordance with the present invention there is provided tissue graftconstructs for orthopaedic and other surgical applications which inexperiments to date have been shown to exhibit many of the desirablecharacteristics important for optimal graft function.

The graft construct in accordance with this invention is prepared from adelaminated segment of intestinal tissue of a warm-blooded vertebrate,the segment comprising the tunica submucosa, the muscularis mucosa andthe stratum compactum of the tunica mucosa. The tunica submucosa,muscularis mucosa and stratum compactum are delaminated from the tunicamuscularis and the luminal portion of the tunica mucosa of the segmentof intestinal tissue. The resulting segment is a tubular, very tough,fibrous, collagenous material which is fully described in U.S. Pat. No.4,902,508 issued Feb. 20, 1990 and U.S. Pat. No. 4,956,178 issued Sep.11, 1990, which patents are expressly incorporated herein by reference.In those patents, the tissue graft material is primarily described inconnection with vascular graft applications.

Intestinal submucosa graft material may be harvested from a biologicalsource such as animals raised for meat production, including, forexample, pigs, cattle and sheep or other warm-blooded vertebrates. Oldersows having a weight between 400 and 600 lbs. have been found to beparticularly good sources of graft material for use for this invention.A graft segment removed from such an older sow can have a tensilestrength of up to 1700 psi in the longitudinal direction of theintestine. Thus, there is a ready source of intestinal submucosa graftmaterial in slaughter houses around the country, ready to be harvestedand utilized in accordance with the present invention.

The tri-layer intestinal segments used to form the graft constructs inaccordance with this invention can be used in their delaminate tubularform or they can be cut longitudinally or laterally to form elongatedtissue segments. In either form, such segments have an intermediateportion and opposite end positions and opposite lateral portions whichcan be formed for surgical attachment to existing physiologicalstructures, using surgically acceptable techniques.

An advantage of the intestinal submucosa graft formed for surgicalrepair in accordance with the present invention is its resistance toinfection. The intestinal submucosa graft material, fully described inthe aforesaid patents, have high infection resistance, long shelf lifeand storage characteristics. It has been found that xenogeneicintestinal submucosa is compatible with hosts following implantation asvascular grafts, ligaments and tendons because of its basic composition.The intestinal submucosa connective tissue is apparently very similaramong species. It is not recognized by the host's immune system as"foreign" and therefore is not rejected. Further the intestinalsubmucosa grafts appear to be extremely resistant to infection becauseof their trophic properties toward vascularization and toward endogenoustissues surgically affixed or otherwise associated with the implantgraft. In fact, most of the studies made with intestinal submucosagrafts to date have involved non-sterile grafts, and no infectionproblems have been encountered. Of course, appropriate sterilizationtechniques acceptable to the Federal Drug Administration (FDA) may wellbe used to treat grafts in accordance with the present invention.

It has been found that unsterilized clean intestinal submucosa graftmaterial can be kept at 4° C. (refrigerated) for at least one monthwithout loss of graft performance. When the intestinal submucosa graftmaterial is sterilized by known methods, it will stay in good conditionfor at least two months at room temperature without any resultant lossin graft performance.

It has also been found that the grafts formed and used in accordancewith this invention upon implantation undergo biological remodelling.They serve as a rapidly vascularized matrix for support and growth ofnew endogenous connective tissue. The graft material used in accordancewith this invention has been found to be trophic for host tissues withwhich it is attached or otherwise associated in its implantedenvironment. In multiple experiments the graft material has been foundto be remodelled (resorbed and replaced with autogenous differentiatedtissue) to assume the characterizing features of the tissue(s) withwhich it is associated at the site of implantation. In tendon andligament replacement studies the graft appears to develop a surface thatis synovialized. Additionally, the boundaries between the graft andendogenous tissue are no longer discernible. Indeed, where a singlegraft "sees" multiple microenvironments as implanted, it isdifferentially remodeled along its length. Thus when used in cruciateligament replacement experiments not only does the portion of the grafttraversing the joint become vascularized and actually grow to look andfunction like the original ligament, but the portion of the graft in thefemoral and tibial bone tunnels rapidly incorporates into and promotesdevelopment of the cortical and cancellous bone in those tunnels. Infact, it has been found that after six months, it is not possible toidentify the tunnels radiographically. It appears that intestinalsubmucosa serves as a matrix for and stimulates bone regrowth(remodeling) within the tunnels. The bone tunnels with the encompassedintestinal submucosa graft have never been shown to be a weak point inthe tensile-strength evaluations after sacrifice of test dogsaccomplished to date.

It is one object of the present invention, therefore, to provide graftconstructs for use as connective tissue substitute, particularly as asubstitute for ligaments and tendons. The graft is formed from a segmentof intestinal tissue of a warm-blooded vertebrate. The graft constructcomprises the tunica submucosa, the muscularis mucosa and the stratumcompactum of the tunica mucosa, said tunica submucosa, muscularis mucosaand stratum compactum being delaminated from the tunica muscularis andthe luminal portions of the tunica mucosa of the segment of intestinaltissue. The graft construct has a longitudinal dimension correspondingto the length of the segment of intestinal tissue and a lateraldimension proportioned to the diameter of the segment of intestinaltissue. For tendon and ligament replacement, applications the resultingsegment is typically preconditioned by stretching longitudinally to alength longer than the length of the intestinal tissue segment fromwhich it was formed. For example, the segment is conditioned bysuspending a weight from said segment, for a period of time sufficientto allow about 10 to about 20% elongation of the tissue segment.Optionally, the graft material can be preconditioned by stretching inthe lateral dimension. (The graft material exhibits similar viscoelasticproperties in the longitudinal and lateral dimensions). The graftsegment is then formed in a variety of shapes and configurations, forexample, to serve as a ligament or tendon replacement or substitute or apatch for a broken or severed tendon or ligament. Preferably, thesegment is shaped and formed to have a layered or even a multilayeredconfiguration with at least the opposite end portions and/or oppositelateral portions being formed to have multiple layers of the graftmaterial to provide reinforcement for attachment to physiologicalstructures, including bone, tendon, ligament, cartilage and muscle. In aligament replacement application, opposite ends are attached to firstand second bones, respectively, the bones typically being articulated asin the case of a knee joint. It is understood that ligaments serve asconnective tissue for bones, i.e.. between articulated bones, whiletendons serve as connective tissue to attach muscle to a bone.

When a segment of intestine is first harvested and delaminated asdescribed above, it will be a tubular segment having an intermediateportion and opposite end portions. The end portions are then formed,manipulated or shaped to be attached, for example, to a bone structurein a manner that will reduce the possibility of graft tearing at thepoint of attachment. Preferably it can be folded or partially everted toprovide multiple layers for gripping, for example, with spiked washersor staples. Alternatively, the segment may be folded back on itself tojoin the end portions to provide a first connective portion to beattached, for example, to a first bone and a bend in the intermediateportion to provide a second connective portion to be attached to asecond bone articulated with respect to the first bone.

For example, one of the end portions may be adapted to be pulled througha tunnel in, for example, the femur and attached thereto, while theother of the end portions may be adapted to be pulled through a tunnelin the tibia and attached thereto to provide a substitute for thenatural cruciate ligament, the segment being adapted to be placed undertension between the tunnels to provide a ligament function, i.e., atensioning and positioning function provided by a normal ligament.

The intestinal submucosa segment, which in its preferred embodimentconsists essentially of the tunica submucosa, muscularis mucosa andstratum compactum, has been found to have good mechanical strengthcharacteristics in the same delaminated tubular form in which it isproduced following the described delamination procedure. It has beenfound that having the stratum compactum layer inside the tubular form ina tendon or ligament graft provides good trophic properties forvascularization. It is believed that grafts used in accordance with thepresent invention with the intestinal segment inverted, i.e., with thestratum compactum on the outside will exhibit like functionality, butfurther testing is required to determine the vascularizationcharacteristics with that structure utilized, for example, as a tendonor ligament graft.

Another object of the present invention is to provide a method forsurgical repair of diseased or damaged tissues connecting first andsecond tissues structures selected from the group consisting of bone,ligament, tendon, cartilage and muscle. The method comprises the step ofattaching the first and second structures to opposite end portions oropposite lateral portions of a tissue graft construct formed inaccordance with the above described embodiments. The graft comprises thetunica submucosa, the muscularis mucosa and the stratum compactum of asegment of intestinal tissue of a warm-blooded vertebrate, said tunicasubmucosa, muscularis mucosa and stratum compactum being delaminatedfrom the tunica muscularis and the luminal portion of the tunica mucosaof said intestinal tissue.

Because grafts used in orthopaedic applications are typically placedunder tension in their surgical installation, it may be preferable tocombine two or even more tissue segments to provide a multi-ply(multi-layered) graft construct. It is another object of the presentinvention, therefore, to provide such grafts in which two or more PG,11intestinal segments are arranged to have their end portions joinedtogether with the joined end portions and/or lateral portions adapted tobe attached to a bone, tendon, ligament or other physiologicalstructure. One method for providing a double intestinal segment may beto pull one tubular segment internally within another segment to providea double-walled tube, the joined ends of which can be attached, forexample, to a bone, tendon or ligament. These doubled segments willprovide enhanced tensile strength and resistance to stretching undertension.

A further object of the present invention is to provide such a graft inwhich one of said end portions is adapted to be pulled through a tunnelin, for example, the femur and attached thereto and the other of saidend portion is adapted to be pulled through a tunnel in the tibia andattached thereto to provide a substitute for the natural cruciateligament, the segment being adapted to be placed under tension betweenthe tunnels to provide a ligament function. Similar procedures can beemployed to provide ligament function to other articulating bones.

Still a further object of the present invention is to provide anorthopaedic graft for use as connective tissue to hold fractured bonepieces together and in proper orientation in the body, the segment beingformed to serve as a fracture wrap about segments of fractured bone andto be attached to the bone.

One other object of this invention is to provide a method for promotingthe healing and/or regrowth of diseased or damaged tissue structures bysurgically repairing such structures with a tissue graft constructprepared from a segment of intestinal submucosal tissue as describedabove. The implanted graft construct is trophic toward vascularizationand differentiated tissue growth and is essentially remodelled to assumethe structural and functional characteristics of the repaired structure.

Other objects and features of the present invention will become apparentas this description progresses.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a lateral view of a knee with a graft in accordance withthe present invention extending through a tunnel through the tibia andwrapped over the top of a femur.

FIG. 2 shows an anterior view of the left stifle showing the graftarrangement of FIG. 1.

FIG. 3 shows an anterior view of the left stifle with a graft inaccordance with the present invention extending through tunnels in boththe tibia and the femur with the end portions of the graft attached byscrews and spiked washers in accordance with standard orthopaedicsurgery practices.

FIG. 4 shows a medial view of the left stifle showing a graft inaccordance with the present invention used as a medial collateralligament replacement with opposite end portions of the graft attached bysutures to existing connective tissues.

FIG. 5 is a fragmentary view showing an achilles tendon with a graftplacement in accordance with the present invention adapted to join abreak in the tendon.

FIG. 6 is a fragmentary perspective view showing the graft of FIG. 5being attached.

FIG. 7 is a sectional view showing how the graft is wrapped twice aboutthe tendon in FIGS. 5 and 6.

FIG. 8 shows a tubular section of the graft folded back on itself toprovide a double thickness of intestinal submucosa segment.

FIG. 9 is a fragmentary perspective view showing a graft segment pulledwithin another graft segment to provide a double-walled or tube-within-atube arrangement.

DETAILED DESCRIPTION OF THE INVENTION

The intestinal submucosa graft of the present invention is harvested anddelaminated in accordance with the description in the prior U.S. Pat.Nos. 4,956,178 and 4,902,508. An intestinal submucosa segment is therebyobtained.

To date, of course, such grafts have been used only on test animals. Thefollowing description is based upon the experimental uses made orcontemplated to date.

In FIGS. 1 and 2, a femur is shown above the tibia with a lateral viewin FIG. 1 and an anterior view of the left stifle in FIG. 2. As bestseen in FIG. 2, a graft 10 is installed through a bone tunnel 12 in thetibia in a fashion well-known in orthopaedic surgery. The end portion ofthe graft 10 is attached as indicated at 14 by a spiked washer and screwarrangement to provide the connection to the tibia. The other endportion of the graft 10 is pulled up through the space between thecondylar portions and wrapped over the lateral femoral condyle to beattached as indicated at 16 by another spiked washer and screwarrangement. It will be appreciated that surgeons will generally 14, 16.place such grafts under tension between connections

The arrangement shown in FIGS. 1 and 2 may well be more adaptable fortesting in dogs than it is for repair of human knees. Thus, FIG. 3 showsa likely human application of the graft 10 extending through alignedtunnels 20, 22 in the femur and tibia with the opposite ends of thegraft 10 being connected by teflon spiked washers and screws asindicated at 14 and 16. Such screws and spiked washers may be replacedwith spiked bone staples or any other type of soft-tissue-to-bonefixation devices commonly used in orthopaedic surgery. When the graft ispulled through the tunnels 20, 22 and placed under tension by theattachments indicated at 14, 16, the graft serves a ligament functionbetween the femur and tibia. The graft also apparently stimulates bonegrowth in the tunnels such that the tunnels close in on the grafts tomake connections which, after a period of time, do not have to besupplemented by the screw and washer arrangements.

FIG. 4 illustrates an intestinal submucosa graft 10 used as a medialcollateral ligament replacement attached by sutures to existing adjacenttissues. Thus lateral edges 23,25 of the tubular graft 10 are sutured tothe posterior oblique ligament 24 and the patellar tendon 26 whileopposite ends 27,29 of graft 10 are sutured to ligament/tendon tissuesassociated with the femur and tibia, respectively. The graft 10 ispreferably placed under moderate tension. As discussed above, the graftmay comprise one or more intestinal segments layered together to provideadditional strength.

FIGS. 5, 6 and 7 show how a segment of intestinal submucosa 30 may beshaped and formed to connect a broken or severed achilles tendon. Thesegment 30 is shown as an elongated sheet, its longest dimensioncorresponding to the longitudinal axis of the intestine from which thesegment is removed. The graft segment has generally parallel sides 32,34 and opposite ends 36, 38. This segment 30 is wrapped about theachilles tendon as shown in FIG. 7 to provide a double wrap ormultilayered intermediate portion with the sides 32, 34 providingmultiple layer opposite end portions for attachment to the enclosedtendon. The manner in which the graft is sutured to the tendon isillustrated in FIG. 6.

FIG. 8 shows the tubular segment of intestinal submucosa 40 folded backon itself to join its end portions 42, 44 to provide a first connectiveportion 46 to be attached, for instance, to a first bone and also toprovide a bend indicated at 48 in the intermediate portion of thesegment 40 to provide a second connective portion to be attached to asecond bone articulated with respect to the first bone. The segmentarrangement in FIG. 8, therefore, illustrates a method of using a doublesegment or multilayered segment of intestinal submucosa tissue inaccordance with this invention.

FIG. 9 illustrates another method in which a segment 60 of intestinalsubmucosa is pulled within another tubular segment 62 of intestinalsubmucosa to provide a dual segment or double segment arrangement havinggreater strength.

Presently, it is believed that forming the present grafts to have thestratum compactum layer of the intestinal submucosa internally, at leastin the intermediate portion, will promote graft vascularization, andtests have been made to establish this fact. It should be recognized,however, that having the stratum compactum on the exterior may functionlikewise to allow or even promote graft vascularization, and futuretests may establish this fact. For instance, it will be appreciated thatthe arrangement shown in FIGS. 5, 6 and 7, the multiwrap arrangement, issuch that the stratum compactum of the outer wrap is against the tunicasubmucosa of the inner wrap.

The grafts may be sterilized using some conventional sterilizationtechniques including glutaraldehyde tanning with glutaraldehyde,formaldehyde tanning at acidic pH, propylene oxide treatment, gammaradiation, and peracetic acid sterilization. A sterilization techniquewhich does not significantly weaken the mechanical strength andmechanical properties of the graft is preferably used. For instance, itis believed that strong gamma radiation may cause loss of strength inthe graft material. Because one of the most attractive features of theseintestinal submucosa grafts is the host-remodelling responses, it isdesirable not to use a sterilization approach which will detract fromthat property.

It is presently believed that a suitable graft material should have auniaxial longitudinal tensile strength of at least 3.5 MPa and a strainof no more than 20% with maximal load; a burst point of at least 300mmHg for a specimen that is originally 100 microns thick and shaped in atube of approximately 3 mm internal diameter; and a porosity that isbetween 0.5 and 3.0 ml at 120 mmHg pressure per square centimeter. Asindicated above, it is presently believed that the most availableappropriate source for such intestinal submucosa graft may be the smallintestine from 400 to 600 lb. sows which are harvested in slaughterhouses. The tubular segments from such sows typically have a diameter ofabout 10 mm to about 15 mm.

The graft material has a characteristic stress-strain relationship.Because orthopedic application of the graft construct will most ofteninvolve stress upon the graft, it is desirable that the graft materialbe "pre-conditioned" by controlled stretching prior to use as aconnective tissue replacement.

One method of "pre-conditioning" involves application of a given load tothe intestinal submucosa graft material for three to five cycles. Eachcycle consists of applying a load of approximately two megapascals tothe graft material for five seconds, followed by a ten second relaxationphase. It has been found that three to five cycles causes approximatelytwenty percent strain. The graft material does not return to itsoriginal size; it remains in a "stretched" dimension.

To date, several studies have been made that relate to orthopaedicapplications of the type described above in connection with the drawingsusing intestinal submucosa harvested from sows. These studies include 14dogs in which intestinal submucosa has been implanted as an anteriorcruciate ligament, six dogs in which intestinal submucosa has beenimplanted as a medial collateral ligament and nine dogs in whichintestinal submucosa has been used as an achilles tendon. In a separatesingle animal, intestinal submucosa has been used as a "fracture wrap".Some of these animals have been euthanized and the grafts harvested forevaluation.

Results of three dogs with anterior cruciate ligament replacements havebeen evaluated to show that the tensile strength of the intestinalsubmucosa graft was at least 70% of the contralateral normal anteriorcruciate ligament (ACL) by 10 weeks post-surgery. These evaluations showthat the graft was approximately three times the thickness at 10 weeksthan it was at the time of the implantation, and it was wellvascularized. The intestinal submucosa ACLs also become covered withsynovium within two to three weeks and incorporate into the bone throughthe bone tunnels extremely rapidly and strongly. The longest survivorsat this time are approximately eight months and appear to be doing well.

Two dogs with the intestinal mucosa medial collateral ligament have alsobeen sacrificed to show aggressive fibroblastic ingrowth at one monthpost-surgery with synovial lining of the articular surface. The graft isattached firmly to the extra-articular aspect of the medial meniscus.There was almost complete restoration of medial stability of the kneewithin four weeks of implantation. At this time, the remaining five dogswith intestinal submucosa medial collateral ligaments are clinicallynormal with no instability.

Three dogs with achilles tendon replacements with intestinal submucosahave been sacrificed. Of the three groups of dogs, this group showed themost visible evidence of graft remodelling (probably because oflocation). The grafts thicken to the normal achilles tendon thicknesswithin approximately four to six weeks and can support the normal weightof the animal without a brace within one month. The remodelledconnective tissue shows extensive vascularization and orientation of thecollagen fibrils along the lines of stress. The only inflammation thatwas present was represented by small accumulations of mononuclear cellsnear the suture material, just as would be seen in any surgical wound.The intestinal submucosa grafts appear to develop a peritenon that issynovialized and the boundary between the normal achilles and theintestinal submucosa graft was no longer recognizable with H&E stainedhistologic tissue sections by 16 weeks post-surgery. Six dogs remain tobe sacrificed in this group and the longest survivor is nowapproximately six months post-implant.

The bone tunnels with the encompassed intestinal submucosa grafts havenever been shown to be the weak point in tensile strength evaluationsafter sacrifice of dogs that have had the intestinal submucosa ACLsurgery. In addition, the test animals have not had any infectionproblem with any of the orthopaedic applications to date.

What is claimed is:
 1. A tendon or ligament graft construct for use asconnective tissue substitute, said graft formed from a segment ofintestinal tissue of a warm-blooded vertebrate, said segment comprisingthe tunica submucosa, the muscularis mucosa, and the stratum compactumof the tunica mucosa, said tunica submucosa, muscularis mucosa andstratum compactum being delaminated from the tunica muscularis and theluminal portion of the tunica mucosa of said segment of intestinaltissue, said graft construct having an intermediate portion and oppositeend portions, said end portions being formed to present multiple segmentlayers for providing reinforcement for attachment of the graft constructto existing physiological structures, said graft construct further beingconditioned for its use as a connective tissue substitute by stretchingso that the graft construct is longer than the segment of intestinaltissue from which it is formed.
 2. The graft construct of claim 1conditioned by stretching so that it is about 10 to about 20 percentlonger than the intestinal segment from which it was formed.
 3. Thegraft construct of claim 1 in which said segment is folded back onitself to join said end portions to provide a first connective portionto be attached to a first physiological structure and a bend in saidintermediate portion to provide a second connective portion to beattached to a second physiological structure.
 4. The graft construct ofclaim 1 in which one of said end portions is adapted to be attached to afirst bone and the other of said end portions is adapted to be attachedto a second bone articulated with respect to said first bone, saidconstruct being conditioned by stretching so that it is longer than thesegment of intestinal tissue from which is was formed so that it can beplaced under tension between said first and second bones to provide aligament function.
 5. A tendon or ligament graft for use as a connectivetissue substitute in both ligament and tendon locations throughout thebody, said graft comprising intestinal tissue of a warm-bloodedvertebrate, said segment comprising the tunica submucosa, the muscularismucosa and the stratum compactum of the tunica mucosa, said tunicasubmucosa, muscularis muscosa and stratum compactum being delaminatedfrom the tunica muscularis and the luminal portion of the tunica mucosaof said segment of intestinal tissue, said graft being formed to have anintermediate portion comprising multiple tissue segment layers, saidintermediate portion terminating with opposite end portions, said endportions being formed for attachment to a bone, tendon or ligament, saidgraft further being conditioned for use as a tendon or ligamentsubstituted by stretching so that the graft is longer than the segmentsof intestinal tissue from which it is formed.
 6. The graft of claim 5conditioned by stretching longitudinally so that it is about 10 to about20 percent longer than the segment of intestinal tissue from which itwas formed.
 7. The graft of claim 5 conditioned by stretching laterallyso that it is wider than the segment of intestinal tissue from which itis formed.
 8. The graft of claim 5 in which said segment is cut andflattened out to provide an elongated sheet extending in thelongitudinal direction of the intestine to have generally parallel sidesand opposite ends, said sheet being rolled up about generally acylindrical axis generally perpendicular to the longitudinal directionto provide said intermediate portion to encose a tendon or ligament,said sides providing said opposite end portions to be attached to saidenclosed tendon or ligament on opposite sides of a break or teartherein.
 9. The graft of claim 8 in which said sheet is rolled up tohave multilayers of said segment for enclosing a ligament or tendon. 10.The graft of claim 1 in which said graft is formed with at least twosuch segments, one pulled within the other to provide a double walledtubular structure with the adjacent end portions joined together.
 11. Atendon or ligament graft material formed from a segment of intestinaltissue, said graft material comprising the tunica submucosa, themuscularis mucosa and the stratum compactum of the tunica mucosa, saidtunica submucosa, muscularis mucosa and stratum compactum beingdelaminated from the tunica muscularis and the luminal portion of thetunica mucosa of said segment of intestinal tissue, and said graftmaterial initially having a longitudinal dimension corresponding to thelength of the segment of intestinal tissue and a lateral dimensionproportioned to the diameter of the segment of intestinal tissue, saidtissue graft material being stretched longitudinally so that it islonger than the segment of intestinal tissue from which it was formed.12. The tendon or ligament graft material of claim 11 stretched to alength about 10 to about 20% longer than the segment of intestinalsegment from which it was formed.
 13. The tendon or ligament graftmaterial of claim 11 wherein the tissue graft material is also stretchedlaterally.